Related Experiment Videos
Cytokine targeting in psoriasis and psoriatic arthritis: beyond TNFalpha
1Division of Immunology, Infection and Inflammation, University of Glasgow, Centre for Rheumatic Diseases, Glasgow, Scotland. i.b.mcinnes@climed.gla.ac.uk
Abstract:
Targeting TNFalpha provided proof of concept for the role of pro-inflammatory cytokines in promoting cutaneous inflammation, particularly psoriasis. Recent studies have elucidated the presence of numerous cytokine and chemokine activities in psoriatic skin and synovium. There is considerable interest in the potential of such activities as novel therapeutic targets. IL-15 is an innate response cytokine that activates leukocyte subsets via binding to its unique IL-15Ralpha and shared beta and gamma chain receptors. IL-15 promotes T cell memory and sustains local T cell activation, in part via prevention of apoptosis and mediates activation of monocytes, neutrophils and NK cells. IL-15 is up-regulated in psoriatic skin and psoriatic arthritis synovium. IL-15 blockade in a murine model of psoriasis led to marked suppression of typical psoriatic skin features. Clinical intervention in other chronic inflammatory disease states is now ongoing with encouraging early efficacy, raising the possibility for the first time of targeting this novel inflammatory moiety in psoriasis.
Insights
Interleukin-15 (IL-15) is a key driver of psoriasis inflammation. Blocking IL-15 shows promise in treating psoriatic skin conditions and related inflammatory diseases.
Area of Science:
- Immunology
- Dermatology
- Cytokine Biology
Background:
- Pro-inflammatory cytokines, like TNFalpha, are validated targets in cutaneous inflammation such as psoriasis.
- Psoriatic skin and synovium exhibit significant cytokine and chemokine activity, presenting novel therapeutic opportunities.
Purpose of the Study:
- To investigate the role of Interleukin-15 (IL-15) as a therapeutic target in psoriasis.
- To evaluate the efficacy of IL-15 blockade in a murine model of psoriasis.
Main Methods:
- Analysis of cytokine and chemokine profiles in psoriatic skin and synovium.
- Assessment of IL-15's role in leukocyte activation, T cell memory, and apoptosis prevention.
- Administration of IL-15 blockade in a murine model of psoriasis.
Main Results:
- IL-15 is upregulated in psoriatic skin and psoriatic arthritis synovium.
- IL-15 blockade in a murine psoriasis model significantly suppressed characteristic skin lesions.
- Early clinical trials targeting IL-15 in other inflammatory diseases show encouraging efficacy.
Conclusions:
- IL-15 is a critical pro-inflammatory cytokine implicated in the pathogenesis of psoriasis.
- Targeting IL-15 presents a promising novel therapeutic strategy for psoriasis and potentially other chronic inflammatory diseases.
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The JAK-STAT Signaling Pathway
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...